Coinfection of SARS-CoV-2 and Other Respiratory Pathogens

Figures & data

Table 1 Demographic and Baseline Characteristics

	CoIV, n (%)	CoIaB, n (%)	P^#
N	18	21
Age in Years, Median (IQR)	45.5 (31.0–67.5)	35.0 (27.0–63.5)	0.210
Sex, Female	10 (55.6)	12 (57.1)	0.921
HCWS	6 (33.3)	7 (33.3)	1.000
Comorbidity	4 (22.2)	8 (38.1)	0.322
Hypertension	3 (16.7)	3 (14.3)	0.837
Coronary Heart Disease	1 (5.6)	3 (14.3)	0.609
Diabetes Mellitus	0 (0)	2 (9.5)	0.490
Malignancy^a	1 (5.6)	1 (4.8)	0.911
COPD	0 (0)	1 (4.8)	0.348
Pregnancy^b	0 (0)	2 (9.5)	0.490
Onset-Symptom
Fever (≥37.3°C)	12 (66.7)	15 (71.4)	0.748
Cough/Sore Throat	13 (33.3)	14 (66.7)	0.742
Shortness of Breath/Dyspnea	9 (50.0)	9 (42.9)	0.752
Expectorate	5 (27.8)	5 (23.8)	0.777
Fatigue	7 (38.9)	1 (4.8)	0.015*
Diarrhea	2 (11.1)	4 (19.0)	0.667
Myalgia	4 (22.2)	2 (9.5)	0.387
Anorexia	3 (16.7)	2 (9.5)	0.647
Nausea/Vomiting	3 (16.7)	1 (4.8)	0.318
Headache/Dizziness	3 (16.7)	1 (4.8)	0.318
Abdominal Pain	3 (16.7)	0 (0)	0.089
Disease Severity Status at Diagnosis
Mild/Moderate	10 (55.6)	10 (47.7)	0.751
Severe/Critical	8 (44.5)	11 (52.4)

Notes: ^#Comparison using Mann–Whitney U-test, Fisher’s Exact test or Χ² test accordingly; *P<0.05. ^aOne was thyroid cancer and the other was acute myeloid leukemia + hematopoietic stem cell transplantation status. ^bTwo women were diagnosed with SARS-CoV-2 infection on day 2 and day 14 postpartum, respectively.

Abbreviations: IQR, interquartile range; CoIV, coinfection of viral pathogen; CoIaB, coinfection of atypical bacterial pathogen; HCWS, health-care workers; COPD, chronic obstruct pulmonary disease.

Table 2 Coinfections in SARS-CoV-2 Patients and the Additional Respiratory Pathogens Identified

Coinfection	n (%)
Additional Pathogen	39 (15.6)
Adenovirus	7 (2.8)
Influenza A Virus	2 (0.8)
Influenza B Virus	1 (0.4)
M. pneumoniae	11 (4.4)
C. pneumoniae	13 (5.2)
Respiratory Syncytial Virus (RSV)	12 (4.8)
Coinfection
One Pathogen	34 (13.6)
Two Pathogens	5 (2.0)
Pathogen Combinations
M. pneumoniae + C. pneumoniae	4 (1.6)
RSV + Adenovirus	1 (0.4)
Coinfection Timing N=39
Prior to SARS-CoV-2	16 (41.0)
Days Prior to SARS-CoV-2, Median (IQR)	3.5 (2.0–8.0)
Simultaneous Detection	7 (17.9)
Post SARS-CoV-2	16 (41.0)
Days post SARS-CoV-2, Median (IQR)	4.5 (2.3–10.0)
Days from Illness Onset to Infection with Additional Respiratory Pathogen, Median (IQR)	11 (5–25)
Days from Illness Onset to SARS-CoV-2 Infection, Median (IQR)	8 (5–26)

Figure 1 Timeline of the detection of respiratory pathogens in patients with a coinfection.

Table 3 Laboratory Findings on Admission

	CoIV (N=18) Median (IQR)	CoIaB (N=21) Median (IQR)	P^#
Laboratory Findings
WBC (10^9 · L^−1), N=39	4.9 (3.3–7.1)	4.9 (4.0–5.9)	0.757
Lymphocytes (10^9 · L^−1), N=39	1.1 (0.9–1.7)	1.3 (1.0–1.8)	0.375
Neutrophils (10^9 · L^−1), N=39	3.0 (2.0–5.1)	3.0 (2.4–4.0)	0.888
CRP (mg/L), N=38	12.3 (4.2–36.0)	8.5 (3.2–13.4)	0.203
PCT (ug/L)<0.5, N (%)	17 (94.4)	20 (95.2)	1.000
PCT (ug/L)≥0.5, N (%)	1 (5.6)	1 (4.8)
LDH (U/L), N=33	213.0 (185.8–316.5)	197.0 (174.0–270.0)	0.229
Amyloid A (mg/L), N=33	66.3 (11.1–370.3)	24.3 (8.4–62.8)	0.207
CK(U/L), N=34	75.0 (50.5–99.3)	55.5 (48.0–85.5)	0.381
IL-2 (pg/mL), N=36	2.4 (2.2–2.7)	2.8 (2.6–3.6)	0.016*
IL-4 (pg/mL), N=36	2.0 (1.5–2.2)	2.5 (1.8–3.7)	0.014*
IL-6 (pg/mL), N=36	7.2 (3.2–15.3)	5.0 (3.0–12.1)	0.411
IL-10 (pg/mL), N=36	3.9 (2.8–4.9)	3.5 (2.8–4.7)	0.788
TNF-α (pg/mL), N=36	2.0 (1.8–2.4)	2.6 (1.9–3.7)	0.041*
IFN-γ (pg/mL), N=36	1.9 (1.6–2.7)	2.3 (1.8–3.3)	0.141
Total T-cells (/ul), N=38	912 (580–1251)	969 (773–1308)	0.254
Below LLN, N (%)	10 (55.6)	10 (47.6)	0.757
CD4+ T-cells (/ul), N=38	576 (378–745)	536 (400–823)	0.726
Below LLN, N (%)	12 (66.7)	13 (61.9)	1.000
CD8+ T-cells (/ul), N=38	296 (171–459)	353 (237–518)	0.144
Below LLN, N (%)	12 (66.7)	11 (52.4)	0.522
B-cells(/ul), N=32	184 (109–238)	128 (88–218)	0.439
Below LLN, N (%)	2 (11.1)	4 (19.0)	0.659
NK-cells(/ul), N=32	57 (34–181)	51 (44–108)	0.777
Below LLN, N (%)	11 (61.1)	14 (66.7)	0.678

Notes: ^#Comparison using Mann–Whitney U-test, Fisher’s Exact test; *P<0.05.

Abbreviations: IQR, interquartile range; CoIV, coinfection of viral pathogen; CoIaB, coinfection of atypical bacteria pathogen; WBC, white blood cell; CRP, c-reactive protein; LDH, lactic dehydrogenase; PCT, procalcitonin; CK, creatine kinase; LLN, lower limits of normal.

Table 4 Treatment and Outcomes Between Coinfection of Viral Pathogens and Coinfection of Bacterial Pathogens

	CoIV (N=18) N (%)	CoIaB (N=21) N (%)	P^#
Antibiotics	13 (72.2)	15 (71.4)	0.956
Azithromycin	1 (5.6)	8 (38.1)	0.023*
Antiviral Treatment	18 (100)	20 (95.2)	0.348
Arbidol (Umifenovir)	17 (94.4)	20 (95.2)	0.911
Oseltamivir	6 (33.3)	5 (23.8)	0.723
Lopinavir/Ritonavir	3 (16.7)	4 (19.0)	0.847
Interferon Inhalation	16 (88.9)	16 (76.2)	0.418
Use of Intravenous Corticosteroids	4 (22.2)	2 (9.5)	0.387
Intravenous Human Immunoglobulin	7 (38.9)	2 (9.5)	0.055
Oxygen Support	13 (72.2)	13 (61.9)	0.734
Nasal Cannula	12 (66.7)	13 (61.9)	0.757
High-flow Nasal Cannula	2 (11.1)	1 (4.8)	0.586
NPPV	1 (5.6)	1 (4.8)	0.911
Outcomes
Discharge	16 (88.9)	21 (100)	0.292
Hospitalization	1 (5.6)	0 (0)
Death	1 (5.6)	0 (0)
Time to negative SARS-CoV-2 Nucleic Acid Test Results^a in Days, Median (IQR)	16.0 (8.5–29.5)	16.0 (10.0–23.0)	0.963
SARS-CoV-2 Nucleic Acid Test Results Turn Negative Within 2 Weeks of Onset	5 (27.8)	6 (28.6)	0.310
Anti-SARS-CoV-2-IgM, N=21	11 (61.1)	10 (47.6)	0.320
Peak IgM (AU/mL), Median (IQR)	55.5 (27.9–192.7)	20.2 (18.2–194.5)	0.475
Anti-SARS-CoV-2-IgG, N=33	16 (88.9)	17 (81.0)	0.238
Peak IgG (AU/mL), Median (IQR)	143.2 (79.5–166.5)	104.4 (79.3–136.0)	0.374
Time from Onset to Antibody Production, Median (IQR)	39.5 (29.8–60.3)	45.0 (32.3–58.8)	0.655
Hospital Length of Stay, in Days, Median (IQR)	24.0 (14.0–30.5)	15.0 (11.5–20.0)	0.027*

Notes: ^#Comparison using Mann–Whitney U-test, Fisher’s Exact test or Χ² test; *P<0.05; ^aInterval between first positive detection of SARS-CoV-2 nucleic acid until second consecutive negative SARS-CoV-2 nucleic acid test.

Abbreviations: IQR, interquartile range; CoIV, coinfection of viral pathogen; CoIaB, coinfection of atypical bacterial pathogen; NPPV, noninvasive positive pressure ventilation.